Biosensors provide an analysis of a biological fluid, such as whole blood, urine, or saliva. Typically, biosensors have a measurement device that analyzes a sample of the biological fluid placed in a sensor strip. The analysis determines the concentration of one or more analytes, such as alcohol, glucose, uric acid, lactate, cholesterol, or bilirubin, in a sample of the biological fluid. The sample of biological fluid may be directly collected or may be a derivative of a biological fluid, such as an extract, a dilution, a filtrate, or a reconstituted precipitate. The analysis is useful in the diagnosis and treatment of physiological abnormalities. For example, a diabetic individual may use a biosensor to determine the glucose level in whole blood for adjustments to diet and/or medication.
Many biosensor systems provide calibration information to the measurement device prior to the analysis. The measurement device may use the calibration information to adjust the analysis of the biological fluid in response to one or more parameters, such as the type of biological fluid, the particular analyte(s), and the manufacturing variations of the sensor strip. The accuracy and/or precision of the analysis may be improved with the calibration information. Accuracy may be expressed in terms of bias of the sensor system's analyte reading in comparison to a reference analyte reading, with larger bias values representing less accuracy, while precision may be expressed in terms of the spread or variance among multiple measurements. If the calibration information is not read properly, the measurement device may not complete the analysis or may make a wrong analysis of the biological fluid.
Biosensors may be designed to analyze one or more analytes and may use different volumes of biological fluids. Some biosensors may analyze a single drop of whole blood, such as from 0.25-15 microliters (μL) in volume. Biosensors may be implemented using bench-top, portable, and like measurement devices. Portable measurement devices may be hand-held and allow for the identification and/or quantification of one or more analytes in a sample. Examples of portable measurement systems include the Ascensia Breeze® and Elite® meters of Bayer HealthCare in Tarrytown, N.Y., while examples of bench-top measurement systems include the Electrochemical Workstation available from CH Instruments in Austin, Tex.
Biosensors may use optical and/or electrochemical methods to analyze the sample of the biological fluid. In some optical systems, the analyte concentration is determined by measuring light that has interacted with a light-identifiable species, such as the analyte or a reaction or product formed from a chemical indicator reacting with the analyte redox reaction. In other optical systems, a chemical indicator fluoresces or emits light in response to the analyte redox reaction when illuminated by an excitation beam. In either optical system, the biosensor measures and correlates the light with the analyte concentration of the biological sample.
In electrochemical biosensors, the analyte concentration is determined from an electrical signal generated by an oxidation/reduction or redox reaction of the analyte when an input signal is applied to the sample. An enzyme or similar species may be added to the sample to enhance the redox reaction. The redox reaction generates an electrical output signal in response to the input signal. The input signal may be a current, potential, or combination thereof. The output signal may be a current (as generated by amperometry or voltammetry), a potential (as generated by potentiometry/galvanometry), or an accumulated charge (as generated by coulometry). In electrochemical methods, the biosensor measures and correlates the electrical signal with the concentration of the analyte in the biological fluid.
Electrochemical biosensors usually include a measurement device that applies an input signal through electrical contacts to electrical conductors of the sensor strip. The conductors may be made from conductive materials, such as solid metals, metal pastes, conductive carbon, conductive carbon pastes, conductive polymers, and the like. The electrical conductors typically connect to working, counter, reference, and/or other electrodes that extend into a sample reservoir. One or more electrical conductors also may extend into the sample reservoir to provide functionality not provided by the electrodes. The measurement device may have the processing capability to measure and correlate the output signal with the presence and/or concentration of one or more analytes in the biological fluid.
In many biosensors, the sensor strip may be adapted for use outside, inside, or partially inside a living organism. When used outside a living organism, a sample of the biological fluid is introduced into a sample reservoir in the sensor strip. The sensor strip may be placed in the measurement device before, after, or during the introduction of the sample for analysis. When inside or partially inside a living organism, the sensor strip may be continually immersed in the sample or the sample may be intermittently introduced to the strip. The sensor strip may include a reservoir that partially isolates a volume of the sample or be open to the sample. Similarly, the sample may continuously flow through the strip or be interrupted for analysis.
Sensor strips may include reagents that react with the analyte in the sample of biological fluid. The reagents may include an ionizing agent to facilitate the redox reaction of the analyte, as well as mediators or other substances that assist in transferring electrons between the analyte and the conductor. The ionizing agent may be an oxidoreductase, such as an analyte specific enzyme, which catalyzes the oxidation of glucose in a whole blood sample. The reagents may include a binder that holds the enzyme and mediator together.
Sensor strips may have one or more encoding patterns that provide calibration information to the measurement device. The calibration information may be identification information indicating the type of sensor strip, the analyte(s) or biological fluid associated with the sensor strip, the manufacturing lot of the sensor strip, or the like. The calibration information may indicate the correlation equations to use, changes to the correlation equations, or the like. Correlation equations are mathematical representations of the relationship between the electrical signal and the analyte in an electrochemical biosensor or between light and the analyte in an optical biosensor. Correlation equations may be implemented to manipulate the electrical signal or light for determination of the analyte concentration. Correlation equations also may be implemented as a program number assignment (PNA) table of slopes and intercepts for the correlation equations, another look-up table, or the like. The measurement device uses the calibration information to adjust the analysis of the biological fluid.
Many measurement devices obtain the calibration information from the encoding pattern either electrically or optically. Some encoding patterns may be read only electrically or only optically. Other encoding patterns may be read electrically and optically.
Electrical encoding patterns usually have one or more electrical circuits with multiple contacts or pads. The measurement device may have one or more conductors that connect with each contact on the encoding pattern of the sensor strip. Typically, the measurement device applies an electrical signal through one or more of the conductors to one or more of the contacts on the encoding pattern. The measurement device measures the output signal from one or more of the other contacts. The measurement device may determine the calibration information from the absence or presence of output signals from the contacts on the encoding pattern. The measurement device may determine the calibration information from the electrical resistance of the output signals from the contacts on the encoding pattern. Examples of sensor strips with electrical encoding patterns may be found in U.S. Pat. Nos. 4,714,874; 5,856,195; 6,599,406; and 6,814,844.
In some electrical encoding patterns, the measurement device determines the calibration information from the absence or presence of different contacts. The contacts may be removed, never formed, or disconnected from other parts of the electrical circuit. If the measurement device measures an output signal from the location of a contact, then the measurement device presumes a contact is present. If the measurement device does not measure an output signal, then the measurement device presumes a contact is absent.
In other electrical encoding patterns, the measurement device determines the calibration information from the resistance of the electrical output signal from the contact. Typically, the amount of conductive material associated with each contact varies, thus changing the electrical resistance. Contacts may have additional or fewer layers of conductive material. The length and thickness of the connection between the contacts and the electrical circuit also may vary. The contacts may be removed, never formed, or disconnected from the electrical circuit.
Optical encoding patterns usually have a sequence of lines and/or array of pads. The measurement device determines the calibration information from the encoding pattern by scanning the encoding pattern to determine the absence or presence of the lines or pads.
Errors may occur with these conventional electrical and optical encoding labels. During manufacturing, shipping, handling, and the like, the sensor strips may acquire or lose material. The additional or missing material may cause the measurement device to obtain the wrong calibration information from the encoding label, which may prevent completion or cause a wrong analysis of the biological fluid.
In electrical encoding patterns, the additional or missing material may change or interfere with the calibration information. The additional material may cover the contacts, the contact locations, or the connections between the contacts. If the additional material is conductive, the measurement device may determine that a contact is present when a contact is absent or may measure an incorrect resistance from a contact. If the additional material is non-conductive, the measurement device may determine that a contact is absent when a contact is present or may measure an incorrect resistance from a contact. Additionally, the missing material may have been part of the contacts or the connections between the contacts. Thus, the missing material may cause the measurement device to determine that a contact is absent when a contact is present or may cause the measurement device to measure an incorrect resistance.
In optical encoding patterns, the additional or missing material may change or interfere with the calibration information. The additional material may cover or obstruct the lines or pads. The additional material may cover or obstruct the gaps or spaces between the lines or pads. The missing material may be part of the lines or pads. The additional or missing material may cause the measurement device to scan altered lines or pads.
Accordingly, there is an ongoing need for improved biosensors, especially those that may provide increasingly accurate and/or precise analyte concentration measurements. The systems, devices, and methods of the present invention overcome at least one of the disadvantages associated with encoding patterns on sensor strips used in biosensors.